Variant chr10-43608632-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145312.4(ZNF485):c.43G>A(p.Asp15Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ZNF485
NM_145312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

Variant links:

Genes affected

ZNF485 (HGNC:23440): (zinc finger protein 485) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF485 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF485	NM_145312.4 linkuse as main transcript	c.43G>A	p.Asp15Asn	missense_variant	3/5	ENST00000361807.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF485	ENST00000361807.8 linkuse as main transcript	c.43G>A	p.Asp15Asn	missense_variant	3/5	1	NM_145312.4	P1	Q8NCK3-1
ZNF485	ENST00000374435.3 linkuse as main transcript	c.43G>A	p.Asp15Asn	missense_variant	3/5	1		P1	Q8NCK3-1
ZNF485	ENST00000430885.5 linkuse as main transcript	c.43G>A	p.Asp15Asn	missense_variant	3/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

251072

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.43G>A (p.D15N) alteration is located in exon 3 (coding exon 2) of the ZNF485 gene. This alteration results from a G to A substitution at nucleotide position 43, causing the aspartic acid (D) at amino acid position 15 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.0034

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

3.1

M;.;M

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.4

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.38

B;.;B

Vest4

0.48

MutPred

0.78

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);

MVP

0.44

MPC

0.15

ClinPred

0.95

GERP RS

3.0

Varity_R

0.40

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over